ethyl (2-methylpropyl)phosphinate | 16259-93-1

• 分子结构分类: 有机化合物 - 有机磷化合物
• 英文名称: ethyl (2-methylpropyl)phosphinate
• 英文别名: isobutyl-phosphinic acid ethyl ester；Isobutyl-phosphinsaeure-aethylester；ethyl isobutylphosphinate；Isobutylphosphinsaeure-ethylester
• CAS: 16259-93-1
• 化学式: C₆H₁₅O₂P
• 分子量: 150.158
• InChiKey: QFHLYCIKQUJPEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.15
• 重原子数：
  9.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  ethyl (2-methylpropyl)phosphinate 在 镍 氨 、 氢气 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 10.0~75.0 ℃ 、10.0 MPa 条件下， 反应 5.0h， 生成
  参考文献：
  名称：

  Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists

  摘要：

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

  DOI：

  10.1021/jm00017a016
• 作为产物：
  描述：

  Diethoxy(2-methylpropyl)phosphane 在 水 、 silica gel 作用下， 以 正己烷 、 乙酸乙酯 为溶剂， 以90 %的产率得到ethyl (2-methylpropyl)phosphinate
  参考文献：
  名称：

  通过 SiO2 促进的水解从 P(OR)3 或 ClP(OR)2 轻松合成 H-次膦酸盐

  摘要：

  H-磷酸盐代表一类有价值的有机磷结构单元和催化配体。现有的合成方法通常与强酸的使用、中间体精细处理的需要以及仅引入对芳基的限制有关。在对粗 R'P(OR) 2中间体的色谱处理过程中观察到的意外 SiO 2促进的水解进行全面研究后，我们开发了一种极其简单且通用的合成路线，从市售格氏试剂和 P （或） 3 .另一种方法涉及使用 ClP(OR) 2代替 P(OR) 3 ，这被证明是制备带有大体积邻位取代基序的空间位阻 ArMgBr 底物的有价值的策略。因此，使用该实用方案以中等至高产率获得了 36 种结构不同的 P-(环)烷基和 P-(杂)芳基H-次膦酸盐库。此外，还检查了CuCl 2介导的P(O)–H键衍生，导致以接近定量的产率形成相应的EtOPhP(O)–X (X = O, N, S)化合物。

  DOI：

  10.1021/acs.joc.4c00760

文献信息

• COLD MENTHOL RECEPTOR-1 ANTAGONISTS
  申请人：Colburn Raymond W.

  公开号：US20120053347A1

  公开（公告）日：2012-03-01

  The invention is directed to TRPM8 antagonists of Formula (I). More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating TRPM8-mediated disorders. Pharmaceutical and veterinary compositions and methods of treating pain and various other disease states or conditions using compounds of the invention are also described.

  这项发明涉及式(I)的TRPM8拮抗剂。更具体地，本发明涉及某些新颖化合物，制备化合物的方法，组合物，中间体及其衍生物，以及治疗TRPM8介导的疾病的方法。还描述了使用本发明化合物治疗疼痛和各种其他疾病状态或病情的药用和兽医组合物及治疗方法。
• Phosphinic acid derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US04988681A1

  公开（公告）日：1991-01-29

  A phosphinic acid derivative represented by the general formula [I], or a pharmaceutically acceptable salt thereof, ##STR1## wherein R.sup.1 represents an alkyl, cycloalkyl or aralkyl group which may be substituted; R.sup.2 and R.sup.5 may be identical or different, and each represents a hydrogen atom, or an ester residue capable of forming a non-toxic ester hydrolyzable in vivo; and A represents a group of the formula ##STR2## wherein R.sup.3 represents an alkyl group, a group of the formula ##STR3## wherein R.sup.30 represents a halogen atom, a carboxyl group, a hydroxyl group, a cycloalkyl group which may be substituted, an aryl group which may be substituted, an arylthio group, a heteroarylthio group which may be substituted, an alkylthio group which may be substituted, an amino group which may be substituted, or a lower alkoxycarbonyl group; R.sup.31 represents a hydrogen atom or a lower alkyl group; and n represents an integer of 0 to 6, a cycloalkyl group which may be substituted or an aryl group which may be substituted; and the double bond at A has a Z-configuration, or a group of the formula ##STR4## wherein R.sup.4 represents a cycloalkyl group which may be substituted. Said phosphinic acid derivative is useful for reducing renal toxicity induced by a carbapenem or penem antibiotic and for inhibiting dipeptidase.

  一种磷酸酯衍生物，其通式表示为[I]，或其药学上可接受的盐，其中：R1代表可以被取代的烷基、环烷基或芳基烷基；R2和R5可以相同也可以不同，分别代表氢原子或能够在体内形成不具毒性的酯水解残基；A代表下式的基团：其中R3代表烷基、下式的基团之一：其中R30代表卤素原子、羧基、羟基、可以被取代的环烷基、可以被取代的芳基、芳硫基、可以被取代的杂环芳硫基、可以被取代的烷硫基、可以被取代的氨基或较低烷氧羰基基团；R31代表氢原子或较低烷基基团；n代表0到6的整数、可以被取代的环烷基或可以被取代的芳基；并且A上的双键具有Z构型，或下式的基团之一：其中R4代表可以被取代的环烷基。该磷酸酯衍生物可用于减少由碳青霉烯或青霉烯类抗生素引起的肾毒性并抑制二肽酶。
• [EN] 2-(MORPHOLIN-4-YL)-1,7-NAPHTHYRIDINES<br/>[FR] 2- (MORPHOLIN -4-YL)-L,7-NAPHTYRIDINES
  申请人：BAYER PHARMA AG

  公开号：WO2016020320A8

  公开（公告）日：2017-04-06
• WO2007/134107
  申请人：——

  公开号：——

  公开（公告）日：——
• Kabatschnik et al., Doklady Akademii Nauk SSSR, 1959, vol. 125, p. 1260
  作者：Kabatschnik et al.

  DOI：——

  日期：——